Immunity to TCR peptides in multiple sclerosis: II. T cell recognition of Vβ5.2 and Vβ6.1 CDR2 peptides

Y. K. Chou, W. J. Morrison, A. D. Weinberg, R. Dedrick, Ruth Whitham, Dennis Bourdette, G. Hashim, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

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Abstract

The biased expression of Vβ5.2 and Vβ6.1 by T cells specific for myelin basic protein (BP) has led to our use of TCR peptides from these V gene sequences to induce anti-TCR immunity in patients with multiple sclerosis (MS). Injection of Vβ5.2-39-59 or Vβ6.1-39-59 peptides significantly increased the peptide specific T cell frequency in 7 of 11 MS patients, often with an accompanying delayed hypersensitivity reaction at the injection site. Here, we validate these cellular immune responses by characterizing TCR peptide specific T cells from an MS patient with biased Vβ5.2 expression in BP reactive T cells before treatment with TCR peptides, and from two MS patients in whom the frequencies of anti-TCR peptide specific T cells were significantly boosted after injection with low doses of TCR peptides. In both cases, T cell lines were established with relative ease, especially after boosting with the peptides. A Vβ5.2-39-59 reactive line responded selectively to the boosting peptide and was restricted by both MHC class I (HLA-B7) and MHC class II (HLA-DR2) molecules. Characterization of 22 clonal isolates revealed that the responding T cells were predominantly activated CD4+CD8(lo), circulating memory cells restricted by either HLA-B7 or HLA- DR2, that utilized mainly Vβ4, Vβ6, Vβ12, and Vβ14, but not Vβ5.2 in their TCR. T cell isolates specific for Vβ6.1-39-59 possessed similar characteristics but contained specificities cross-reactive with an N-terminal sequence on Vβ5.2-39-59. Upon stimulation with peptide or Con A, the TCR peptide specific T cell lines had increased message production for IFN-γ, GM-CSF, IL-4, IL-5, and to a lesser degree, IL-2. This lymphokine mRNA profile differed from a BP-specific T cell line that produced message for IFN-γ and GM-CSF but low or absent levels of IL-4 and IL-5. The extensive parallels between human T cells specific for Vβ5.2 and Vβ6.1 CDR2 peptides and rat T cells specific for Vβ8.2 CDR2 peptide that are highly protective against experimental encephalomyelitis strengthen the rationale for the therapeutic use of TCR peptides in human autoimmunity.

Original languageEnglish (US)
Pages (from-to)2520-2529
Number of pages10
JournalJournal of Immunology
Volume152
Issue number5
StatePublished - Mar 1 1994

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Multiple Sclerosis
Immunity
T-Lymphocytes
Peptides
Peptide T
HLA-DR2 Antigen
HLA-B7 Antigen
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Line
Interleukin-4
Injections
Encephalomyelitis
Myelin Basic Protein
Lymphokines
Delayed Hypersensitivity
Therapeutic Uses
Autoimmunity
Cellular Immunity
Interleukin-2

ASJC Scopus subject areas

  • Immunology

Cite this

Immunity to TCR peptides in multiple sclerosis : II. T cell recognition of Vβ5.2 and Vβ6.1 CDR2 peptides. / Chou, Y. K.; Morrison, W. J.; Weinberg, A. D.; Dedrick, R.; Whitham, Ruth; Bourdette, Dennis; Hashim, G.; Offner, Halina; Vandenbark, Arthur.

In: Journal of Immunology, Vol. 152, No. 5, 01.03.1994, p. 2520-2529.

Research output: Contribution to journalArticle

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abstract = "The biased expression of Vβ5.2 and Vβ6.1 by T cells specific for myelin basic protein (BP) has led to our use of TCR peptides from these V gene sequences to induce anti-TCR immunity in patients with multiple sclerosis (MS). Injection of Vβ5.2-39-59 or Vβ6.1-39-59 peptides significantly increased the peptide specific T cell frequency in 7 of 11 MS patients, often with an accompanying delayed hypersensitivity reaction at the injection site. Here, we validate these cellular immune responses by characterizing TCR peptide specific T cells from an MS patient with biased Vβ5.2 expression in BP reactive T cells before treatment with TCR peptides, and from two MS patients in whom the frequencies of anti-TCR peptide specific T cells were significantly boosted after injection with low doses of TCR peptides. In both cases, T cell lines were established with relative ease, especially after boosting with the peptides. A Vβ5.2-39-59 reactive line responded selectively to the boosting peptide and was restricted by both MHC class I (HLA-B7) and MHC class II (HLA-DR2) molecules. Characterization of 22 clonal isolates revealed that the responding T cells were predominantly activated CD4+CD8(lo), circulating memory cells restricted by either HLA-B7 or HLA- DR2, that utilized mainly Vβ4, Vβ6, Vβ12, and Vβ14, but not Vβ5.2 in their TCR. T cell isolates specific for Vβ6.1-39-59 possessed similar characteristics but contained specificities cross-reactive with an N-terminal sequence on Vβ5.2-39-59. Upon stimulation with peptide or Con A, the TCR peptide specific T cell lines had increased message production for IFN-γ, GM-CSF, IL-4, IL-5, and to a lesser degree, IL-2. This lymphokine mRNA profile differed from a BP-specific T cell line that produced message for IFN-γ and GM-CSF but low or absent levels of IL-4 and IL-5. The extensive parallels between human T cells specific for Vβ5.2 and Vβ6.1 CDR2 peptides and rat T cells specific for Vβ8.2 CDR2 peptide that are highly protective against experimental encephalomyelitis strengthen the rationale for the therapeutic use of TCR peptides in human autoimmunity.",
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